Objective: To characterize longitudinal trajectories of testicular development in boys and breast development in girls, so as to provide reference data for understanding patterns of pubertal sexual maturation. Methods: Based on the Shanghai Pudong New Area Cohort Study on Growth, Development and Health in Children and Adolescents, a baseline survey was conducted in 2020 using a mult stage cluster random sampling method. A total of 2 184 children who completed all follow ups during the primary school period from 13 elementary schools in Pudong New Area,Shanghai,with annual follow ups during 2021-2025. Testicular volume and Tanner stage of breast development were assessed by professional physicians using standardized visual inspection and palpation. The age distribution of testicular volume and breast development was fitted by using cumulative link mixed models and Turnbull s nonparametric maximum likelihood estimation method. Results: Median ages for testicular volumes of 2, 3, 4 and 5 mL in boys were 7.07, 9.24, 10.29, and 11.57 years old, respectively. Median ages for Tanner breast stages Ⅱ, Ⅲ, Ⅳ, and Ⅴ in girls were 8.55 , 10.17, 11.18, and 13.78 years old, respectively. Based on overweight and obesity, stratified analysis showed that earlier pubertal onset among overweight/obesity children, and the key milestones for pubertal initiation were testicular volume reaching 4 mL in boys and breast Tanner II in girls for 10.29, 10.83; 8.18, 9.00 years. Conclusion Overweight and obesity are associated with earlier pubertal initiation,but there are certain gender and developmental stage specific patterns.

Objective: To investigate the molecular mechanism of Syk in phagocytosis induced by CD36 antibodies. Methods: In vitro, two CD36 monoclonal antibodies, GZ1 (IgG2a) and GZ4 (IgG1), at different concentrations were co-incubated with platelets from CD36-positive blood donors, and the affinity of the antibodies for platelets was assessed using flow cytometry. CD36 positive platelets from donors were labeled with Red-SE. The GZ1 and GZ4 antibodies were added together with dye-labeled platelets to peripheral blood from blood donors for phagocytosis experiments. The expression of the Spleen Tyrosine Kinase (Syk), P-Syk, P38 MAPK and P-P38 were detected using Western blot(WB). In the in vitro phagocytosis inhibition assay, Fcγ receptor (FcγR) antibodies or Syk inhibitor (R406) were pre-incubated with monocytes prior to performing the phagocytosis experiment. In vivo experiments were performed using female C57BL/6J mice. R406 was administered via intraperitoneal injection, followed by tail vein infusion of GZ1 or GZ4 antibodies. Additionally, a treatment group was set up in which the antibodies were infused first, followed by administration of R406. Changes in platelet counts were analyzed using a blood routine analyzer, and antibody binding to platelets was detected by flow cytometry. Results: GZ1 had higher affinity for CD36positive platelets than GZ4. The phagocytosis rate induced by GZ1 was significantly higher than that of GZ4 [(42.12±2.25)% vs (16.25±6.45)%, P<0.001]. Moreover, GZ1-mediated platelet phagocytosis mainly depends on FcγRⅠ of monocytes, while GZ4-mediated platelet phagocytosis mainly relies on FcγRⅡ of monocytes. WB results showed that the GZ1 group significantly upregulated the expression of Syk and phosphorylated Syk (P-Syk), and induced phosphorylation of the downstream P38 MAPK signaling pathway. Pretreatment of monocytes with R406 inhibited the phagocytosis of antibodyopsonized platelets by monocytes. After injecting GZ1 or GZ4 antibodies into C57BL/6 female mice through the tail vein, GZ1 mAbs had a stronger binding rate to the platelets compared with GZ4 mAbs, leading to a significant decrease in platelet count. After pre-injecting R406 into mice, the platelet count reduction in both the GZ1 and GZ4 groups was alleviated, and the binding rate of antibodies to platelets was also significantly reduced. However, administration of R406 after antibody injection failed to prevent the decrease in platelet counts in mice. Conclusion: This study indicates that Syk plays an important role in the phagocytosis of anti-CD36 opsonized platelets by monocytes/macrophages and is closely associated with the activation of the P38 MAPK signaling pathway.

ObjectiveMagnetoencephalography (MEG), a non-invasive neuroimaging technique, meticulously captures the magnetic fields emanating from brain electrical activity. Compared with MEG based on superconducting quantum interference devices (SQUID), MEG based on optically pump magnetometer (OPM) has the advantages of higher sensitivity, better spatial resolution and lower cost. However, most of the current studies are clinical studies, and there is a lack of animal studies on MEG based on OPM technology. Pain, a multifaceted sensory and emotional phenomenon, induces intricate alterations in brain activity, exhibiting notable sex differences. Despite clinical revelations of pain-related neuronal activity through MEG, specific properties remain elusive, and comprehensive laboratory studies on pain-associated brain activity alterations are lacking. The aim of this study was to investigate the effects of inflammatory pain (induced by Complete Freund’s Adjuvant (CFA)) on brain activity in a rat model using the MEG technique, to analysis changes in brain activity during pain perception, and to explore sex differences in pain-related MEG signaling. MethodsThis study utilized adult male and female Sprague-Dawley rats. Inflammatory pain was induced via intraplantar injection of CFA (100 μl, 50% in saline) in the left hind paw, with control groups receiving saline. Pain behavior was assessed using von Frey filaments at baseline and 1 h post-injection. For MEG recording, anesthetized rats had an OPM positioned on their head within a magnetic shield, undergoing two 15-minute sessions: a 5-minute baseline followed by a 10-minute mechanical stimulation phase. Data analysis included artifact removal and time-frequency analysis of spontaneous brain activity using accumulated spectrograms, generating spectrograms focused on the 4-30 Hz frequency range. ResultsMEG recordings in anesthetized rats during resting states and hind paw mechanical stimulation were compared, before and after saline/CFA injections. Mechanical stimulation elevated alpha activity in both male and female rats pre- and post-saline/CFA injections. Saline/CFA injections augmented average power in both sexes compared to pre-injection states. Remarkably, female rats exhibited higher average spectral power 1 h after CFA injection than after saline injection during resting states. Furthermore, despite comparable pain thresholds measured by classical pain behavioral tests post-CFA treatment, female rats displayed higher average power than males in the resting state after CFA injection. ConclusionThese results imply an enhanced perception of inflammatory pain in female rats compared to their male counterparts. Our study exhibits sex differences in alpha activities following CFA injection, highlighting heightened brain alpha activity in female rats during acute inflammatory pain in the resting state. Our study provides a method for OPM-based MEG recordings to be used to study brain activity in anaesthetized animals. In addition, the findings of this study contribute to a deeper understanding of pain-related neural activity and pain sex differences.

The development and validation of clinical prediction models based on artificial intelligence (AI) and machine learning methods have become increasingly widespread. However, the prediction model bias risk and applicability evaluation tool developed in 2019 (i.e., PROBAST-2019) has shown significant limitations. Therefore, an expanded and updated version of the PROBAST-2019 tool was released in 2025, known as the PROBAST+AI tool. The tool is divided into two parts including model development and model evaluation. It aims to comprehensively and systematically evaluate potential methodological quality issues in model development, bias risks in model evaluation, and the applicability of models, regardless of the modeling method used. This paper provides a systematic interpretation of the PROBAST+AI tool's items and case analyses, with the aim of guiding and assisting researchers engaged in related studies and promoting the high-quality development of clinical predictive model research.

OBJECTIVE: To examine the mechanistic of organochlorine-associated changes in lung function. METHODS: This study investigated 76 healthy older adults in Jinan, Shandong Province, over a five-month period. Personal exposure to organochlorines was quantified using wearable passive samplers, while inflammatory factors and thyroid hormones were analyzed from blood samples. Participants' lung function was evaluated. After stratifying participants according to their thyroid hormone levels, we analyzed the differential effects of organochlorine exposure on lung function and inflammatory factors across the low and high thyroid hormone groups. Mediation analysis was further conducted to elucidate the relationships among organochlorine exposures, inflammatory factors, and lung function. RESULTS: Bis (2-chloro-1-methylethyl) ether (BCIE), was negatively associated with forced vital capacity (FVC, -2.05%, 95% CI: -3.11% to -0.97%), and associated with changes in inflammatory factors such as interleukin (IL)-2, IL-7, IL-8, and IL-13 in the low thyroid hormone group. The mediation analysis indicated a mediating effect of IL-2 (15.63%, 95% CI: 0.91% to 44.64%) and IL-13 (13.94%, 95% CI: 0.52% to 41.07%) in the association between BCIE exposure and FVC. CONCLUSION Lung function and inflammatory factors exhibited an increased sensitivity to organochlorine exposure at lower thyroid hormone levels, with inflammatory factors potentially mediating the adverse effects of organochlorines on lung function.
Environmental Exposure ; Hydrocarbons, Chlorinated/metabolism* ; China ; Ethyl Ethers/metabolism* ; Environmental Monitoring ; Thyroid Hormones/blood* ; Lung/physiology* ; Inhalation Exposure/statistics & numerical data* ; Air Pollution/statistics & numerical data* ; Air Pollutants/metabolism* ; Humans ; Male ; Female ; Middle Aged ; Aged

In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.

Objective To compare the effect of small optical zone orthokeratology lenses(OK lenses)and repeated low-level red-light(RLRL)therapy in controlling myopia progression for adolescents,and the therapeutic effectiveness of RLRL is evaluated.Methods A retrospective analysis was conducted on the clinical data of 80 adolescent myopic patients in the First Affiliated Hospital of Army Medical University.The patients were divided into the RLRL group and the OK lenses group according to different intervention methods,with 40 cases in each group.Patients in the RLRL group received RLRL therapy combined with single-vision spectacles,and patients in the OK lenses group were treated with OK lenses.The changes of spherical equivalent(SE),axial length and subfoveal choroidal thickness(SFCT)1,3,6,and 12 months after treatment compared with the baseline,and color vision of patients were assessed.Based on the mean baseline axial length of the RLRL group,the patients in this group were subdivided into the short axial group and the long axial group,and the changes of the axial length and SFCT were further analyzed.Results The diopter 1,3,6,and 12 months after treatment in the RLRL group were not significantly different from the baseline(P>0.05).Axial lengths of patients in the RLRL group progressively shortened after treatment and returned close to the baseline 12 months after treatment.In contrast,axial lengths of patients in the OK lens continued to grow within 12 months after treatment;the axial lengths at each time point after treatment of patients in the two groups were significantly different from the baseline(P<0.05).The changes of axial length of patients in the RLRL group at each time point after treatment were significantly smaller than those in the OK lenses group(P<0.05).The SFCT changes of patients in the RLRL group at each time point after treatment were all greater than those in the OK lenses group(P<0.05).The SFCT at each time point after treatment in the RLRL group were significantly different from the baseline(P<0.05),whereas the SFCT at each time point after treatment in the OK lenses group were not significantly different from the baseline(P>0.05).The changes of axial length at each time point after treatment of patients in the long axial group were all greater than those in the short axial group(P<0.05);the SFCT changes 6 months after treatment of patients in the long axial group was greater than that in the short axial group(P<0.05);the SFCT at each time point after treatment of patients in the two groups were signifi-cantly different from the baseline(P<0.05).Color vision tests revealed no abnormities after treatment in the RLRL group and the OK lenses group.Conclusion RLRL therapy is effective in controlling myopia progression and demonstrates superior axial length control compared to orthokeratology lenses.

This research aims to construct a stable epithelial cell senescence model for screening and e-valuation of senolytics.We explored the optimal conditions for doxorubicin-induced senescence of non-transformed epithelial cells MCF 10A,including the optimal induction concentration,the optimal inter-vention time,and the optimal senescence duration,and confirmed the feasibility of MCF 10A as an epi-thelial senescence model by multiple ways.The optimal condition for Doxorubicin-induced senescence of MCF 10A cells was treatment with 0.6 μmol/L Doxorubicin for 16 h to achieve the best senescence state on the 8th day.Under the optimal induction conditions,the positive rate of senescence-associated β-gal-actosidase(SA-β-gal)staining in the treated group reached 97％.At the same time,biochemical results of detecting the expression of mRNA,proteins,and immunofluorescence demonstrated that the expression levels of senescence-associated secretory phenotype(SASP),p16,p21 and p53 in the treated group were significantly higher than those in the control cells,and Lamin B1 was significantly decreased(P＜0.001),which were consistent with the specific characteristics of senescence.In summary,an epithelial senescence model was successfully induced in MCF 10A cells by Doxorubicin in this study,which will promote the screening of senolytics for senescent epithelial cells.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.